This is a proposal to study the rate of renin release by superficial and deep juxtraglomerular apparatuses (JGA's) in vivo and in vitro. And to define the role of the sympathetic outflow to the kidney in the control of renin content in outer and inner cortex. The preparation of the studies of regional renin release in vivo is the cat kidney, with its unique venous drainage. Separate sampling of superficial and deep cortical outflows will be combined with measurements of regional renal plasma flow with the aid of radiolabeled micropheres. In rats with chronic unilateral renal denervation the renin content of outer and inner cortex of the ipsilateral kidney will be compared to that of the contralateral organ. Renin release in vitro will be measured in outer and inner cortical slices seeking to establish differences in their responses to different concentrations of catecholamines in the presence and absence of Alpha-adrenergic antagonists. It is also planned to attempt the identification of Alpha-adrenergic receptors by radioligand binding in concentrates of JGA's from superficial and deep cortex. The purpose of the proposed experiments in these preparations is to establish whether there are differences in the response of superficial and deep JGA's to sympathetic impulses. And toi test the hypothesis that Alpha-adrenoreceptors mediate inhibitory influences on JGA's, but that they are exclusively or predominantly distributed in the deep JGA's. Evidence of regional differences in the responses of JGA's to the sympathetic would be of physiological, pharmacological and clinical relevance. The cat kidney preparation itself has a potential for the exploration of regional nephronal functions such as the extraction of various plasma components. Among these, the extraction of insulin combined with estimates of regional plasma flow would make the glomerular filtration rate of deep nephrons accessible to direct measurement.